Antigen-Guided Synthetic Receptor Engineering for Safer T Cell Immunotherapy in Solid Tumors
- 1College of Pharmacy, Dongduk Women’s University, Seoul 02748, Korea .
Abstract
Engineered T cell therapies have transformed cancer immunotherapy, yet their application to solid tumors remains limited by Ag heterogeneity, shared Ag expression in normal tissues, immunosuppressive tumor microenvironments, and immune-mediated toxicities. These barriers indicate that improving cytotoxic potency alone is insufficient. Instead, therapeutic precision depends on how engineered T cells interpret antigenic and immunological context. We discuss solid tumor Ag biology as a determinant of receptor selection, therapeutic efficacy, and on-target off-tumor toxicity. We then examine chimeric Ag receptor, TCR-based, TCR-mimic, soluble TCR, T cell Ag couplers, TCR fusion constructs, and synthetic TCR and Ag receptor/HLA-independent TCR (STAR/HIT) systems with emphasis on Ag accessibility and signaling architecture. We further summarize toxicity mechanisms, including systemic inflammatory amplification, Ag distribution-dependent tissue injury, TCR cross-reactivity, and receptor-associated signaling dysregulation. Finally, we review programmable strategies, including logic-gated receptors, synthetic Notch circuits, quantitative Ag sensing, adaptor-controlled receptors, and genome editing, as approaches for spatial, temporal, and quantitative control. This Ag-guided framework provides a structured basis for matching Ag biology with receptor architecture and safety-control strategies, while emphasizing the need for careful translational evaluation in solid tumor T cell therapy.
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BibTeX
@article{kang2026antigenguided,
title = {{Antigen-Guided Synthetic Receptor Engineering for Safer T Cell Immunotherapy in Solid Tumors}},
author = {Su-Jin Kang and Hyo Jung Cho and Ji-Hyeon Kim and Hyang-Mi Lee},
journal = {Immune Network},
year = {2026},
month = sep,
doi = {10.4110/in.2026.26.e40},
url = {https://doi.org/10.4110/in.2026.26.e40},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Antigen-Guided Synthetic Receptor Engineering for Safer T Cell Immunotherapy in Solid Tumors
AU - Su-Jin Kang
AU - Hyo Jung Cho
AU - Ji-Hyeon Kim
AU - Hyang-Mi Lee
PY - 2026
DA - 2026/09/14
JO - Immune Network
DO - 10.4110/in.2026.26.e40
UR - https://doi.org/10.4110/in.2026.26.e40
AB - Engineered T cell therapies have transformed cancer immunotherapy, yet their application to solid tumors remains limited by Ag heterogeneity, shared Ag expression in normal tissues, immunosuppressive tumor microenvironments, and immune-mediated toxicities. These barriers indicate that improving cytotoxic potency alone is insufficient. Instead, therapeutic precision depends on how engineered T cells interpret antigenic and immunological context. We discuss solid tumor Ag biology as a determinant of receptor selection, therapeutic efficacy, and on-target off-tumor toxicity. We then examine chimeric Ag receptor, TCR-based, TCR-mimic, soluble TCR, T cell Ag couplers, TCR fusion constructs, and synthetic TCR and Ag receptor/HLA-independent TCR (STAR/HIT) systems with emphasis on Ag accessibility and signaling architecture. We further summarize toxicity mechanisms, including systemic inflammatory amplification, Ag distribution-dependent tissue injury, TCR cross-reactivity, and receptor-associated signaling dysregulation. Finally, we review programmable strategies, including logic-gated receptors, synthetic Notch circuits, quantitative Ag sensing, adaptor-controlled receptors, and genome editing, as approaches for spatial, temporal, and quantitative control. This Ag-guided framework provides a structured basis for matching Ag biology with receptor architecture and safety-control strategies, while emphasizing the need for careful translational evaluation in solid tumor T cell therapy.
SN - 1598-2629
SN - 2092-6685
ER -